21636-40-8

Usage

Uses

Used in Pharmaceutical Industry:
11-Piperazinyldibenz[b,f][1,4]oxazepine is used as an active pharmaceutical ingredient for the treatment of neuropsychiatric diseases. Its application in this field is due to its ability to modulate various neurotransmitter systems in the brain, which can help alleviate symptoms associated with these conditions.
Used in Research and Development:
In addition to its therapeutic applications, 11-Piperazinyldibenz[b,f][1,4]oxazepine is also utilized in research and development for the study of neuropsychiatric diseases and the development of new drugs targeting these conditions. Its unique chemical structure and pharmacological properties make it a valuable tool for understanding the underlying mechanisms of these diseases and for designing more effective treatments.
Used in Drug Metabolism Studies:
As a metabolite of Loxapine, 11-Piperazinyldibenz[b,f][1,4]oxazepine plays a crucial role in drug metabolism studies. Understanding the metabolic pathways and the effects of 11-Piperazinyldibenz[b,f][1,4]oxazepine can help researchers optimize drug dosages, minimize side effects, and improve the overall safety and efficacy of Loxapine and other related medications.

Upstream product

• 110-85-0 piperazine 
• 62469-61-8 11-chloro-dibenz<1,4>oxazepine 
• 666818-15-1 2-fluoro-N-(2-hydroxyphenyl)-benzamide 
• 95-55-6 2-amino-phenol 
• 445-29-4 o-fluoro-benzoic acid 
• 3158-85-8 10H-dibenzo[b,f][1,4]oxazepin-11-one 
• 88-73-3 2-Chloronitrobenzene 
• 119-36-8 methyl salicylate 
• 1493-27-2 ortho-nitrofluorobenzene 
• 171103-28-9 2-amino-2'-methyl diphenyl ether carboxylate 
• 92164-06-2 2-nitro-2'-methyl diphenyl ether carboxylate 

Relevant academic research and scientific papers

Dibenzo[b,f][1,4]oxazepines and dibenzo[b,e]oxepines: Influence of the chlorine substitution pattern on the pharmacology at the H1R, H4R, 5-HT2AR and other selected GPCRs

Inspired by VUF6884 (7-Chloro-11-(4-methylpiperazin-1-yl)dibenzo[b,f][1,4]oxazepine), reported as a dual H1/H4 receptor ligand (pKi: 8.11 (human H1R (hH1R)), 7.55 (human H4R (hH4R))), four known and 28 new oxazepine and related oxepine derivatives were synthesised and pharmacologically characterized at histamine receptors and selected aminergic GPCRs. In contrast to the oxazepine series, within the oxepine series, the new compounds showed high affinity to the hH1R (pKi: 6.8–8.7), but no or moderate affinity to the hH4R (pKi: ≤ 5.3). For one oxepine derivative (1-(2-Chloro-6,11-dihydrodibenzo[b,e]oxepin-11-yl)-4-methylpiperazine), the enantiomers were separated and the R-enantiomer was identified as the eutomer at the hH1R (pKi: 8.83 (R), 7.63 (S)) and the guinea-pig H1R (gpH1R) (pKi: 8.82 (R), 7.41 (S)). Molecular dynamic studies suggest that the tricyclic core of the compounds is bound in a similar mode into the binding pocket, as described for doxepine in the hH1R crystal structure. Moreover, docking studies of all oxepine derivatives at the hH1R indicate that the oxygen and the position of the chlorine in the tricyclic core determines, if the R- or the S-enantiomer is the eutomer. For some of the oxazepines and oxepines the affinity to other aminergic GPCRs is in the same range as to hH1R or hH4R, thus, those compounds have to be classified as dirty drugs. However, one oxazepine derivative (3,7-Dichloro-11-(4-methylpiperazin-1-yl)dibenzo[b,f][1,4]oxazepine was identified as dual hH1/h5-HT2A receptor ligand (pKi: 9.23 (hH1R), 8.74 (h5-HT2AR), ≤7 at other analysed GPCRs), whereas one oxepine derivative (1-(3,8-Dichloro-6,11-dihydrodibenzo[b,e]oxepin-11-yl)-4-methylpiperazine) was identified as selective hH1R antagonist (pKi: 8.44 (hH1R), ≤6.7 at other analyzed GPCRs). Thus, the pharmacological results suggest that the oxazepine/oxepine moiety and additionally the chlorine substitution pattern toggles receptor selectivity and specificity.

AMINO SUBSTITUTED DIARYL[A,D]CYCLOHEPTENE ANALOGS AS MUSCARINIC AGONISTS AND METHODS OF TREATMENT OF NEUROPSYCHIATRIC DISORDERS

Disclosed herein are analogs of clozapine and pharmaceutically acceptable salts, esters, amides, or prodrugs thereof; methods of synthesizing the analogs; and methods of using the analogs for treating neuorpsychiatric disorders. In some embodiments, the analogs are amino substituted diaryl[a,d]cycloheptenes.

Synthesis and evaluation of antipsychotic activity of 11-(4-aryl-1- piperazinyl)-dibenz [b, f][1,4] oxazepines and their 8-chloro analogues

Atypical drugs reduce positive and negative symptoms of schizophrenia, without inducing EPS, but they exert other undesirable side effects. We have gone for synthesis of novel derivatives of Loxapine which are devoid of catalepsy and have decreased metabolic demethylation which is the prominent factor for bioavailability of the drug. While doing so we have also been successful in retaining the antipsychotic activity of the drug. Condensation of 8,11-dichlorodibenzoxazepine and 11-chlorodibenzoxazepine with 1-aryl piperazines was carried to give 8-chloro-11-(4-aryl-1-piperazinyl)-dibenz[b,f] [1,4]oxazepines and 11-(4-aryl-1-piperazinyl)-dibenz[b,f][1,4]oxazepines respectively. These derivatives were found as active as Clozapine.

Loxapine analogs and methods of use thereof

The invention relates to novel compounds and methods of using them for modulating sleep.

USE OF N-DESMETHYLCLOZAPINE AND RELATED COMPOUNDS AS DOPAMINE STABILIZING AGENTS

Disclosed herein is the use of N-desmethylclozapine (NDMC) and related compounds to treat a variety of neuropsychiatric diseases including psychosis. It is shown that NDMC and related compounds are agonists or partial agonists at D2 and D3 dopamine receptors and thus may be effective as a dopamine stabilizing agent, allowing it to be used to treat or provide reduced incidence of Extrapyramidal symptoms (EPS) and/or tardive dyskinesias (TD). Also disclosed is administering NDMC and related compounds in combination with other anti-psychotic agents.

AMINO SUBSTITUTED DIARYL[A,D]CYCLOHEPTENE ANALOGS AS MUSCARINIC AGONISTS AND METHODS OF TREATMENT OF NEUROPSYCHIATRIC DISORDERS

Disclosed herein are analogs of clozapine and pharmaceutically acceptable salts, esters, amides, or prodrugs thereof; methods of synthesizing the analogs; and methods of using the analogs for treating neuorpsychiatric disorders. In some embodiments, the analogs are amino substituted diaryl[a,d]cycloheptenes.

ALKYL-SUBSTITUTED COMPOUNDS HAVING DOPAMINE RECEPTOR AFFINITY

Described herein are D4 receptor-selective compounds of the general formula: STR1 wherein: A and B are independently selected, optionally substituted, unsaturated 5-or 6-membered, homo-or heterocyclic rings; X 1 is selected from CH 2, O, NH, S, C. dbd.O, CH--OH, CH--N(C 1-4 alkyl) 2, C=CHCl, C=CHCN, N--C 1-4 alkyl, N-acetyl, SO 2 and SO;X 2---is selected from N=, CH 2--, CH= and C(O);Y is selected from N and CH;R. sub.1 represents C 1-4 alkyl;n is 0, 1 or 2;q is 1 or 2; andZ is C 5-10 alkyl optionally substituted with OH, halo, C 1-4 alkyl or C 1-4 alkoxy and optionally incorporating a heteroatom selected from O, N and S;and acid addition salts, solvates and hydrates thereof. Their use as ligands for dopamine receptor identification and in a drug screening program, and as pharmaceuticals to treat indications in which D4 receptor stimulation is implicated, such as schizophrenia, is also described.

ALKYL-SUBSTITUTED COMPOUNDS HAVING DOPAMINE RECEPTOR AFFINITY

Described herein are D4 receptor-selective compounds of the general formula: STR1 wherein: A and B are independently selected, optionally substituted, saturated or unsaturated 5-or 6-membered, homo-or heterocyclic rings;X 1 is selected from CH 2, O, NH, S, C=O, CH--OH, CH--N(C 1-4 alkyl) 2, C=CHCl, C= CHCN, N--C 1-4 alkyl, N-acetyl, SO 2 and SO;X. sub.2 . . . is selected from N=, CH 2--, CH=, C(O)--, O--, and S--;Y is selected from N and CH; R. sub.1 represents C 1-4 alkyl;n is 0, 1 or 2;q is 1 or 2; andZ is C 5-10 alkyl optionally substituted with OH, halo, C 1-4 alkyl or C 1-4 alkoxy and optionally incorporating a heteroatom selected from O, N and S; and acid addition salts, solvates and hydrates thereof. Their use as ligands for dopamine receptor identification and in a drug screening program, and as pharmaceuticals to treat indications in which the D4 receptor is implicated, such as schizophrenia, is also described.